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Genetic variability revealed in malaria genomes newly sequenced by two multi-national research teams points to new challenges in efforts to eradicate the parasite, but also offers a clearer and more detailed picture of its genetic composition, providing an initial roadmap in the development of pharmaceuticals and vaccines to combat malaria.

The research appears in two studies published in the latest issue of the journal Nature Genetics. They focus on Plasmodium vivax (P. vivax), a species of malaria that afflicts humans and the most prevalent human malaria parasite outside Africa, and Plasmodium cynomolgi (P. cynomolgi), a close relative that infects Asian Old World monkeys.

“The bad news is there is significantly more genetic variation in P. vivax than we’d thought, which could make it quite adept at evading whatever arsenal of drugs and vaccines we throw at it,” said Professor Jane Carlton, senior author on both studies and part of New York University’s Center for Genomics and Systems Biology. “However, now that we have a better understanding of the challenges we face, we can move forward with a deeper analysis of its genomic variation in pursuing more effective remedies.”

In one study, the researchers examined P. vivax strains from different geographic locations in West Africa, South America, and Asia, providing the researchers with the first genome-wide perspective of global variability within this species. Their analysis showed that P. vivax has twice as much genetic diversity as the world-wide Plasmodium falciparum (P. falciparum) strains, revealing an unexpected ability to evolve and, therefore, presenting new challenges in the search for treatments.

The second study, performed jointly with Professor Kazuyuki Tanabe at Osaka University, Japan, sequenced three genomes of P. cynomolgi. The researchers compared its genetic make-up to P. vivax and to Plasmodium knowlesi (P. knowlesi), a previously sequenced malaria parasite that affects both monkeys and humans in parts of Southeast Asia.

Their work marked the first time P. cynomolgi genomes have been sequenced, allowing researchers to identify genetic diversity in this parasite. Its similarity to P. vivax means that their results will also benefit future efforts to understand and fight against forms of malaria that afflict humans.

“We have generated a genetic map of P. cynomolgi, the sister species to P. vivax, so we can now push forward in creating a robust model system to study P. vivax,” explained Tanabe. “This is important because we can’t grow P. vivax in the lab, and researchers desperately need a model system to circumvent this.”

Much of the work occurred under a seven-year grant from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The funding has established 10 International Centers of Excellence for Malaria Research (ICEMR). Carlton is heading an ICEMR based in India, where malaria – and P. vivax in particular -- is a significant public health burden. A particular aim of this Center of Excellence is to support and help train scientists in India who can then work to combat infectious diseases, such as malaria, where they are most prominent. The P. vivax sequencing was funded by NIAID as part of the NIAID funded Genomic Sequencing Center for Infectious Diseases at the Broad Institute under Contract No. HHSN272200900018C. The Burroughs Wellcome Fund was instrumental in providing pilot funds for the P. cynomolgi sequencing.

Researchers at the following institutions were also part of the P. vivax sequencing: The Broad Institute, the National Institute of Malaria Research in India, Arizona State University, and the Centers for Disease Control and Prevention.

Researchers at the following institutions were also part of the work on P. cynomolgi: Osaka University, Dokkyo Medical University, Japan’s Corporation for Production and Research of Laboratory Primates, Nagasaki University, Juntendo University’s School of Medicine, the University of Tokyo, the National Institute of Biomedical Innovation, the Centers for Disease Control and Prevention, and Arizona State University.

Researchers have recently sequenced genomes of malaria that afflict humans (P. vivax) and, shown above, Asian Old World monkeys (P. cynomolgi). Their results point to new challenges in efforts to eradicate the parasite, but also offer a clearer and more detailed picture of its genetic composition, providing an initial roadmap in the development of pharmaceuticals and vaccines to combat malaria. (Image courtesy of Dr. Ananias Escalante, Arizona State University).